It is useful to isolate one or more particular types of particles in a biological fluid sample in an automated fashion at the point-of-care in many applications of healthcare and medical research, such as sample analysis for diagnosis and monitoring purposes. These particles include cells, proteins, nucleic acids and other molecules commonly found in biological fluid. In one example, early detection of tumor cells circulating in the blood of a cancer-afflicted patient may help alert clinicians to tumor progression before the cancer metastasizes and spreads to other parts of the body, and could provide a surrogate marker for monitoring successful treatment response. In another example, detection of circulating endothelial cells and endothelial progenitor cells may help clinicians monitor new blood vessel formation in both normal processes (e.g. wound healing, revascularization after cerebral ischemia or myocardial infarction) and abnormal pathological processes (e.g. tumor growth, vascular malformations).
There are several conventional setups used for particle isolation from biological fluids. However, conventional particle isolation systems are slow and inefficient, cannot be done in an automated fashion at the patient bedside, and result in outputs that are less pure and lead to inaccurate analyses. Conventional particle isolation systems are also limited in their ability to isolate rare particle populations (e.g. rare cells and proteins) from complex fluid tissue samples. For example, immuno-modified magnetic nanoparticle (nanobead)-based separation, which selectively isolates phenotypically identical cells based on their affinity and binding to specific antibodies and/or a magnetic field, is not suitable for detection or isolation of rare cells such as tumor cells due to its poor efficiency. Problems related to efficiency and purity can be attributed to analyzing samples with a non-uniform distribution of particles during particle isolation, poor labeling with immuno-modified nanobeads, a non-uniform magnetic field within a macroscale test tube or container during magnetic enrichment, and an inability to process samples in a continuous flow through format. Conventional setups that are slow, less efficient, and result in less pure samples limit accuracy of resulting analysis of isolated cells, and limits the throughput and number of target rare cells that can be isolated.
Isolation of particles from biological fluids is also at the core of medical treatment using dialysis systems, which process biological fluids with semipermeable membranes that filter substances from the fluid prior to recirculation back to its source. These systems suffer from the nonselective nature of semipermeable membranes and the inability to target specific particles for removal. As such, there is a demand for a point-of-care device in which the system is capable of selectively removing specific particles from the biological fluid, while returning the remaining processed fluid back to its source.
Thus, there is a need in the medical field to create an improved system and method for isolating particles from biological fluid at the point-of-care. This invention provides such an improved system and method.